Neural stem cells have the ability to differentiate into neurons, astrocytes and oligodendrocytes. Recent advances in neural stem cell biology have shown that such stem cells can be isolated, expanded, and used as source material for brain transplants (Snyder, E. Y. et al. Cell 68, 33-51 (1992); Rosenthal, A. Neuron 20, 169-172 (1998); Gage, F. H., et al. Ann. Rev. Neurosci. 18, 159-192 (1995); Weiss, S. et al. Trends Neurosci. 19, 387-393 (1996); Snyder, E. Y. et al. Clin. Neurosci. 3, 310-316 (1996); Martinez-Serrano, A. et al. Trends Neurosci. 20, 530-538 (1997); McKay, R. Science 276, 66-71 (1997); Studer, L. et al. Nature Neurosci. 1, 290-295 (1998)). However, although multiple studies demonstrate that implanted neural stem cells successfully engraft and assume legitimate neural phenotypes, when transplanted into the intact adult brain these cells seem biased toward astro- and oligodendroglial fates (Martínez-Serrano, A. et al. Trends Neurosci. 20, 530-538 (1997); McKay, R. Science 276, 66-71 (1997); Snyder, E. Y. et al. Proc. Natl. Acad. Sci. USA 94, 11663-11668 (1997)).
Most neurodegenerative diseases affect neuronal populations. Moreover, most of the damage occurs to a specific neurochemical phenotype. In human Parkinson's disease, for example, the major cell type lost is midbrain dopaminergic neurons. Functional replacement of specific neuronal populations through transplantation of neural tissue represents an attractive therapeutic strategy for treating neurodegenerative diseases (Rosenthal, A. Neuron 20, 169-172 (1998))